Sara Piva, PT, PhD. is Assistant Professor in the Department of Physical Therapy at the University of Pittsburgh. She is an academic Physical Therapist with a Master of Science degree in Musculoskeletal PT and a Ph.D. in Rehabilitation Sciences. Her goal is to become an independent investigator fully qualified in design and implementation of clinical and translational investigations on the effectiveness of rehabilitation to improve muscle function and maximize functional outcome in patients with arthritis. During this KO1 award, she will pursue bench training in the assessment of morphological and metabolic muscle adaptations in response to neuromuscular electrical stimulation (NMES) in patients with rheumatoid arthritis (RA). The candidate will gain skills in assessing skeletal muscle composition with computerized tomography (CT) imaging, and performing histo- and biochemical analyses of quadriceps muscle samples to assess muscle fiber type, fat content, and oxidative capacity (mitochondria content and enzyme activity). This training will make the candidate uniquely cross-trained in clinical and basic science to undertake a comprehensive approach to study muscle rehabilitation. Through the help of her mentors, Dr. Delitto, Dr. Goodpaster, Dr. Wasko, and Dr. Fitzgerald, and through a combination of practical training, coursework, directed readings, participation in symposia, collaboration with consultants, and the implementation of the research proposed in this KO1, the candidate will gain the necessary skills for a career as an independent investigator and fill an important research gap. The primary aim of the research plan is to determine the effect of NMES on functional outcome and muscle hypertrophy in individuals with RA. The secondary aim is to determine the mechanism by which NMES affects muscle hypertrophy and physical function. After baseline testing, 60 individuals with RA will be randomly assigned to a 16-week NMES program or highly intense volitional exercise program. Both programs will be applied based on the best current clinical evidence. Subjects will be re-assessed after intervention. Groups will be compared for differences in performance-based and self-reported lower extremity function, muscle volume, muscle strength, proportion and area of type I and II muscle fibers, fat content, and muscle oxidative capacity from pre- to post-intervention. Changes in physical function, muscle volume, and muscle strength will be correlated with proportion and area of type I and II muscle fibers, fat content, and markers of muscle oxidative capacity. The internationally recognized research environment of the University of Pittsburgh will highly contribute to the development of Dr. Piva's career.